Prostate cancer is the most common cancer and the second leading cause of cancer death affecting men in the United States. Approximately 30% of men with detectable serum prostate-specific antigen (PSA) levels after curative radical prostatectomy have local recurrences while about 40% are expected to have distant disease. The remaining 30% of men with PSA relapse will not have detectable disease based on standard imaging methods. The need for an accurate imaging-based method as a tool for detecting the disease early becomes obvious in this clinical setting of major public health concern. If the disease is localized in the prostate fossa, salvage radiation therapy may be considered. In men with metastatic prostate cancer, androgen deprivation (surgical or medical) at the time of PSA relapse remains to be the cornerstone of treatment. Encouraging results from preliminary studies at our laboratory and ancillary results from other researchers have prompted us to investigate the potential diagnostic utility of positron emission tomography (PET) with [F- 18]-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (F-18 FMAU) in the imaging evaluation of prostate cancer. FMAU, first developed in our laboratory, is a thymidine analog that is phosphorylated by thymidine kinase and incorporated in the DNA and therefore is useful for imaging tumor proliferation. F-18 FMAU has no or very little accumulation in bone and in urinary bladder that renders it as a potentially ideal PET radiotracer for imaging in prostate cancer. We propose in this preclinical translational molecular imaging project to systematically study the level and extent of F-18 FMAU uptake in metastatic, localized xenograft as well as orthotopic animal models of human prostate cancer using microPET imaging. We will also examine the correlations among the tumor uptake level and the underlying key molecular markers (proliferation index, Ki-67 and androgen receptor, AR). Our project will form the solid foundation that is needed for future diagnostic imaging clinical trials of F-18 FMAU in men with prostate cancer, specifically in the large group of men who present with biochemical failure and by definition have no localizable disease based on standard imaging studies. PUBLIC HEALTH RELEVANCE: Prostate cancer is a growing public health problem as the most common cancer and the second leading cause of cancer death affecting men in the United States. Early detection of recurrent and metastatic disease allows early appropriate treatment that can then help in enhancing quality of life and overall survival. Our animal project is based on positron emission tomography (PET) with an agent specific for tumor proliferation (F-18 FMAU) forming the solid foundation that is needed for future imaging clinical trials in the large group of men who present with PSA relapse and no localizable disease based on current standard imaging studies.